P564: FINAL RESULTS OF THE QOLESS AZA-AMLE RANDOMIZED TRIAL TO EVALUATE THE EFFICACY OF 5-AZA FOR POST-REMISSION THERAPY OF ACUTE MYELOID LEUKEMIA IN ELDERLY PATIENTS
Authors: E. N. Oliva, P. Salutari, F. Di Raimondo, G. Reda, D. Capelli, G. Iannì, G. Tripepi, C. Alati, C. Mammì, M. G. D’Errigo, P. Niscola, C. Selleri, P. Musto, E. Vigna, A. Volpe, N. Cascavilla, M. C. Cannatà, D. Mannina, A. Candoni
Journal: HemaSphere (2022)

Background: Elderly patients in complete remission (CR) after first-line therapy for acute myeloid leukemia (AML) relapse within months unless additional therapy is given. In elderly patients with AML in CR after intensive chemotherapy, the HOVON 97 study reported on the efficacy and safety of azacitidine (5-Aza) post-remission therapy and the randomized QUAZAR trial showed that CC-486 as maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo. We report final results of the QoLESS AZA-AMLE Phase III, randomized, open label, Italian multicentre, trial to evaluate the efficacy of 5-Aza for post-remission therapy of elderly AML patients compared to best supportive care (BSC). Aims: The primary endpoint is disease-free survival (DFS, from CR to relapse/death at 2 and 5 years. Secondary endpoints are post-remission hospitalizations, overall survival (OS) at 2 and 5 years and changes in quality of life (QoL). Methods: Patients aged ≥ 61 years with untreated AML, “de novo” or evolving from MDS, fit for intensive chemotherapy but ineligible for stem cell transplantation received induction chemotherapy consisting of 2 courses of 3 + 7 (Daunorubicin 40 mg/m2 daily days 1-3 and cytarabine 100 mg/m2 intravenous infusion days 1-7. Cases in CR received cytarabine 800 mg/m2 3-hour infusion twice daily for 3 days. Patients in CR were randomized to receive BSC or 5-Aza 50 mg/m2 for 7 days every 28 days and dose increase after 1st cycle to 75 mg/m2 for further 5 cycles, followed by cycles every 56 days for 4.5 years. QoL was assessed with QOL-E version 3 and EORTC QLQ-C30 version 3.0. Results: 149 patients were enrolled to finally randomize 54 patients alive and in CR (Table 1). After randomization, no patients died before relapse, 7 cases completed the study while 43 subjects relapsed: at 2 years, 22 cases in BSC (median DFS: 6.0 months, 95% CI: 0.2–11.7) versus 18 in the 5-Aza arm (median DFS: 10.8 months, 95% CI: 1.9-19.6; p=0.20); at 5 years, 1 subject on BSC withdrew consent and 23 subjects relapsed (median DFS: 6.0 months, 95% CI: 0.2–11.7) while 2 subjects on 5-Aza withdrew consent, 1 discontinued for bladder cancer and 20 relapsed (median DFS: 10.8 months, 95% CI: 1.9-19.6; p=0.23). Age modified the effect of the allocation arm on DFS. Data adjustment for cytogenetic risk further amplified the efficacy of 5-Aza in patients aged >68 years, both at 2 (HR: 0.24, 95% CI: 0.08-0.69, P=0.008) and 5 years (HR: 0.28, 95% CI: 0.10-0.76, P=0.012). The effect of 5-Aza versus BSC tended to be statistically significant on DFS at 2 (P=0.053) and 5 years (P=0.068) in Cox models including cytogenetic risk and MRD as covariates. Kaplan-Meier analyses of the effect of 5-Aza on DFS (at 2 and 5 years) showed that patients aged >68 years and positive MRD tended to have a benefit in terms of DFS at both 2 and 5 years (P=0.056). In the 5-Aza arm, 5 subjects out of 27 (19%) were hospitalised whereas no patient was hospitalised in the BSC arm (P=0.023). QoL was similar in both arms after randomization. Twenty grade 3-4 adverse events, mainly neutropenia, occurred in 5-Aza versus 1 in BSC arm (p=0.002). Image:Summary/Conclusion: 5-Aza is well tolerated in elderly patients with AML who have achieved CR following standard chemotherapy. MRD remains an important predictor of DFS in the long-term, independent of 5-Aza maintenance. No statistically significant differences were observed between the two arms in terms of DFS, but after data adjustment it is suggested that patients aged >68 years and positive MRD may benefit from 5-Aza maintenance.